eIF4EHP promotes Ldh mRNA translation in and fruit fly adaptation to hypoxia.

Hypoxia induces profound modifications in the gene expression program of eukaryotic cells due to lowered ATP supply resulting from the blockade of oxidative phosphorylation. One significant consequence of oxygen deprivation is the massive repression of protein synthesis, leaving a limited set of mRNAs to be translated. Drosophila melanogaster is strongly resistant to oxygen fluctuations; however, the mechanisms allowing specific mRNA to be translated into hypoxia are still unknown. Here, we show that Ldh mRNA encoding lactate dehydrogenase is highly translated into hypoxia by a mechanism involving a CA-rich motif present in its 3' untranslated region. Furthermore, we identified the cap-binding protein eIF4EHP as a main factor involved in 3'UTR-dependent translation under hypoxia. In accordance with this observation, we show that eIF4EHP is necessary for Drosophila development under low oxygen concentrations and contributes to Drosophila mobility after hypoxic challenge. Altogether, our data bring new insight into mechanisms contributing to LDH production and Drosophila adaptation to oxygen variations.

Does ICU admission dysphagia independently contribute to delirium risk in ischemic stroke patients? Results from a cohort study.

BACKGROUND: Delirium is prevalent in ischemic stroke patients, particularly those in the intensive care unit (ICU), and it poses a significant burden on patients and caregivers, leading to increased mortality rates, prolonged hospital stays, and impaired cognitive function. Dysphagia, a common symptom in critically ill patients with ischemic stroke, further complicates their condition. However, the association between dysphagia and delirium in this context remains unclear. The objective of this study was to investigate the correlation between dysphagia and delirium in ICU patients with ischemic stroke. METHODS: A retrospective analysis was conducted on adult patients diagnosed with ischemic stroke at a medical center in Boston. Ischemic stroke cases were identified using the ninth and tenth revisions of the International Classification of Diseases. Dysphagia was defined as a positive bedside swallowing screen performed by medical staff on the day of ICU admission, while delirium was assessed using the ICU Confusion Assessment Method and review of nursing notes. Logistic regression models were used to explore the association between dysphagia and delirium. Causal mediation analysis was employed to identify potential mediating variables. RESULTS: The study comprised 1838 participants, with a median age of approximately 70 years, and 50.5% were female. Among the total study population, the prevalence of delirium was 43.4%, with a higher prevalence observed in the dysphagia group (60.7% vs. 40.8%, p < 0.001) compared to the non-dysphagia group. After adjusting for confounding factors including age, sex, race, dementia, depression, sedative medications, history of falls, visual or hearing deficit, sequential organ failure score, and Glasgow coma score, multifactorial logistic regression analysis demonstrated a significant association between dysphagia and an increased likelihood of delirium (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 1.07-2.05; p = 0.018; E-value = 1.73). Causal mediation analysis revealed that serum albumin levels partially mediated the association between dysphagia and delirium in critically ill patients with ischemic stroke (average causal mediated effect [ACME]: 0.02, 95% CI: 0.01 to 0.03; p < 0.001). CONCLUSION: ICU admission dysphagia may independently contribute to the risk of delirium in patients with ischemic stroke. Early identification and intervention in ischemic stroke patients with dysphagia may help mitigate the risk of delirium and improve patient prognosis.

Effects of gender-affirming hormone therapy on body fat: a retrospective case‒control study in Chinese transwomen.

BACKGROUND: There is insufficient research on how gender-affirming hormone therapy (GAHT) affects body fat modifications in transwomen from China. It is unclear whether hormone therapy affects the prevalence of obesity and blood lipid levels within this population. The current research aimed to assess how GAHT and treatment duration had an impact on the change in and redistribution of body fat in Chinese transwomen. METHODS: This study included 40 transwomen who had not received GAHT and 59 who had. Body fat, blood lipid, and blood glucose levels were measured. GAHT is mainly a pharmacologic (estrogen and anti-androgen) treatment. The study also stratified participants based on the duration of GAHT to assess its impact on body fat distribution. The duration of GAHT was within one year, one to two years, two to three years, or more than three years. RESULTS: After receiving GAHT, total body fat increased by 19.65%, and the percentage of body fat increased by 17.63%. The arm, corrected leg, and leg regions showed significant increases in fat content (+ 24.02%, + 50.69%, and + 41.47%, respectively) and percentage (+ 25.19%, + 34.90%, and + 30.39%, respectively). The total visceral fat content decreased (-37.49%). Based on the diagnostic standards for a body mass index ≥ 28 or total body fat percentage ≥ 25% or 30%, the chance of developing obesity did not change significantly. Blood glucose levels significantly increased (+ 12.31%). Total cholesterol levels (-10.45%) decreased significantly. Fat changes in those who received GAHT for one to two years were significantly different from those who did not receive GAHT. CONCLUSION: After receiving GAHT, total body fat and regional fat increased in Chinese transwomen, and the body fat distribution changed from masculine to feminine, especially during the first two years. However, neither the increase in total body fat percentage nor the decrease in visceral fat content didn't bring about significant changes in the incidence of obesity, nor did triglycerides or low-density lipoprotein-cholesterol.

Ergothioneine: an underrecognised dietary micronutrient required for healthy ageing?

Ergothioneine is a naturally occurring amino acid and thiol antioxidant found in high amounts in mushrooms and fermented foods. Humans and animals acquire ergothioneine from the diet through the pH-dependent activity of a membrane transporter, the large solute carrier 22A member 4 (SLC22A4), expressed on the apical membrane of the small intestine. The SLC22A4 transporter also functions in the renal reabsorption of ergothioneine in the kidney, with avid absorption and retention of ergothioneine from the diet observed in both animals and humans. Ergothioneine is capable of scavenging a diverse range of reactive oxygen and nitrogen species, has metal chelation properties, and is predicted to directly regulate nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Although not lethal, the genetic knockout of the SLC22A4 gene in multiple organisms increases susceptibility to oxidative stress, damage and inflammation; in agreement with a large body of preclinical data suggesting the physiological function of ergothioneine is as a cellular antioxidant and cytoprotectant agent. In humans, blood levels of ergothioneine decline after the age of 60 years, and lower levels of ergothioneine are associated with more rapid cognitive decline. Conversely, high plasma ergothioneine levels have been associated with significantly reduced cardiovascular mortality and overall mortality risks. In this horizon's manuscript, we review evidence suggesting critical roles for dietary ergothioneine in healthy ageing and the prevention of cardiometabolic disease. We comment on some of the outstanding research questions in the field and consider the question of whether or not ergothioneine should be considered a conditionally essential micronutrient.

Protective effects of Bifidobacterium bifidum FL-228.1 on dextran sulfate sodium-induced intestinal damage in mice.

PURPOSE: Numerous studies have found that probiotics benefit the intestinal barrier. However, the prophylactic effects of probiotics on the intestinal barrier, i.e., if probiotics exert protective effects in healthy individuals to defend them against harmful elements, have seldomly been reported. The present study aimed to investigate the possible mechanisms of potential strains with the function of preventing intestinal barrier damage. METHODS: This study investigated nine potential probiotic strains using in vitro and in vivo models on their intestinal barrier-protecting properties. Transcriptomic was then employed to decipher the underlying mechanisms of action of the strains. RESULTS: The results showed that the strains, to varying degrees, regulated the ratio of interleukin (IL)-10 and IL-12 in peripheral blood mononuclear cells (PBMCs), increased the transepithelial electrical resistance (TEER) values, and decreased Caco-2 cell monolayers permeability. Correspondingly, the strains showed different prophylactic efficacies in protecting mice from dextran sulfate sodium (DSS)-induced intestinal barrier damage. Remarkably, Bifidobacterium bifidum FL-228.1 (FL-228.1) showed the best prophylactic efficacies in protecting mice from DSS-induced intestinal barrier damage. Further research suggested that FL-228.1 exerted its prophylactic effects by enhancing mucin 2 (Muc2) production and Claudin (Cldn)-4 in the colon. Furthermore, the transcriptomic and protein-protein interactions (PPI) analyses indicated that the inhibition of NLRP3 and the activation of PPARγ and TLR2 could be involved in protecting the intestinal barrier by FL-228.1. CONCLUSION: Bifidobacterium bifidum FL-228.1 may be developed as a promising probiotic for the prevention of intestinal barrier damage via PPARγ/NLRP3/ TLR2 pathways by enhancing Muc2 and Cldn-4.

The effects of medicinal and food homologous substances on blood lipid and blood glucose levels and liver function in patients with nonalcoholic fatty liver disease: a systematic review of randomized controlled trials.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disorder worldwide. According to several previous studies, the treatment of patients with NAFLD using medicinal and food-homologous substances has consistent effects on the levels of blood lipids and blood glucose and liver function. OBJECTIVE: This systematic review was conducted to investigate the impact of medicinal and food homologous substances on blood lipid and glucose levels as well as liver function in patients with NAFLD. METHODS: A thorough search was conducted in eight databases, including China Science and Technology Journal Database (VIP), Chinese National Knowledge Infrastructure(CNKI), China Biomedical Literature Database (SinoMed), Wanfang Database, PubMed, Cochrane Library, Web of Science and Embase, for articles published from database inception until June 24, 2023. The methodological quality of the included studies was evaluated utilizing Cochrane Randomized Trial Risk Bias Tool, Edition 2 and GRADE methodology for assessment. RESULTS: A total of 13 randomized controlled trials, involving 829 patients with NAFLD, were included in the analysis, these studies included a total of 9 medicinal and food homologous substances. In the 13 studies, hawthorn (2), sea buckthorn (1), ginger (2), turmeric (4) (1 with chicory seeds), cinnamon (1), cardamom (1), purslane (1) and saffron (1) were included. The results of the included studies showed that medicinal and food homologous substances could improve high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TGs), fasting blood glucose (FBG) and liver enzyme levels in patients with NAFLD to a certain extent, but the effect of turmeric on TC, liver enzyme levels is controversial. CONCLUSION: In patients with NAFLD, dietary intervention using medicinal and food homologous substances can ameliorate blood lipid and blood glucose levels and liver enzymes to some extent. In clinical work, medicinal and food homologous substances can be used to provide patients with NAFLD with a safe and effective dietary plan to help prevent and treat disease onset and progression.

Gain-of-function mutations in ALPK1 cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome.

OBJECTIVES: To test the hypothesis that ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache) syndrome, caused by dominant mutation in ALPK1, is an autoinflammatory disease. METHODS: This cohort study systematically evaluated 27 patients with ROSAH syndrome for inflammatory features and investigated the effect of ALPK1 mutations on immune signalling. Clinical, immunologic and radiographical examinations were performed, and 10 patients were empirically initiated on anticytokine therapy and monitored. Exome sequencing was used to identify a new pathogenic variant. Cytokine profiling, transcriptomics, immunoblotting and knock-in mice were used to assess the impact of ALPK1 mutations on protein function and immune signalling. RESULTS: The majority of the cohort carried the p.Thr237Met mutation but we also identified a new ROSAH-associated mutation, p.Tyr254Cys.Nearly all patients exhibited at least one feature consistent with inflammation including recurrent fever, headaches with meningeal enhancement and premature basal ganglia/brainstem mineralisation on MRI, deforming arthritis and AA amyloidosis. However, there was significant phenotypic variation, even within families and some adults lacked functional visual deficits. While anti-TNF and anti-IL-1 therapies suppressed systemic inflammation and improved quality of life, anti-IL-6 (tocilizumab) was the only anticytokine therapy that improved intraocular inflammation (two of two patients).Patients' primary samples and in vitro assays with mutated ALPK1 constructs showed immune activation with increased NF-κB signalling, STAT1 phosphorylation and interferon gene expression signature. Knock-in mice with the Alpk1 T237M mutation exhibited subclinical inflammation.Clinical features not conventionally attributed to inflammation were also common in the cohort and included short dental roots, enamel defects and decreased salivary flow. CONCLUSION: ROSAH syndrome is an autoinflammatory disease caused by gain-of-function mutations in ALPK1 and some features of disease are amenable to immunomodulatory therapy.

Evaluating the effects of simulated interprofessional teaching on the development of clinical core competence in nursing students: a mixed methods study.

BACKGROUND: While single-method studies have reported on the effectiveness of simulated interprofessional teaching, our understanding of its full effects remains incomplete. Teaching design also provides no relevant theoretical guidance, which reduces the scientific quality and rigor of research. The purpose of this work was to study the effects of the simulated interprofessional education (SIPE) teaching model based on the 3P theory on the course of "Clinical Critical Thinking Training" through a convergent mixed method, and to provide the basis for future teaching design. METHODS: A convergent mixed-method design was used, which consisted of a survey and a semi-structured interview. Data collection took place from September 2021 to July 2022. A cluster sampling method was used to select 60 full-time nursing students from a school in China, and randomly divide them into a control group of 36 and an experimental group of 24. According to the principle of voluntary participation, 6 students majoring in clinical medicine and 6 students majoring in pharmacy were recruited to join the experimental group to form an interprofessional team. The students studied "Clinical Critical Thinking Training" together, in which the control group used traditional simulation teaching and the experimental group used SIPE. The CCTDI (California Critical Thinking Disposition Inventory) and AITCS-II Student (Assessment of Interprofessional Team Collaboration in Student Learning Scale) were used for quantitative evaluation before and after the course, and descriptive statistics and Mann-Whitney U test were used to compare the critical thinking and interprofessional collaboration skills of the two groups of students. Semi-structured interviews were used for qualitative evaluation. Thematic analysis was used to understand student development on the basis of inter-professional core competencies and learning experience. RESULTS: The students' interprofessional cooperation abilities and critical thinking scores improved compared with the beginning of the course, but the scores of the experimental group were significantly higher than the control group (p < 0.05). Three themes emerged regarding simulated interprofessional teaching: clarifying team positioning, improving team efficiency, and optimizing the learning experience. CONCLUSION: SIPE can build students' critical thinking, teamwork, and interprofessional core competencies, which makes it a useful teaching design.

Chemoselective and Diastereoselective Synthesis of C-Aryl Nucleoside Analogues by Nickel-Catalyzed Cross-Coupling of Furanosyl Acetates with Aryl Iodides.

Canonical nucleosides are vulnerable to enzymatic and chemical degradation, yet their stable mimics-C-aryl nucleosides-have demonstrated potential utility in medicinal chemistry, chemical biology, and synthetic biology, although current synthetic methods remain limited in terms of scope and selectivity. Herein, we report a cross-electrophile coupling to prepare C-aryl nucleoside analogues from readily available furanosyl acetates and aryl iodides. This nickel-catalyzed modular approach is characterized by mild reaction conditions, broad substrate scope, excellent ß-selectivity, and high functional-group compatibility. The exclusive chemoselectivity with respect to the aryl iodide enables efficient preparation of a variety of C-aryl halide furanosides suitable for various downstream transformations. The practicality of this transformation is demonstrated through the synthesis of a potent analogue of a naturally occurring NF-κB activator.

Farnesoid X receptor knockout protects brain against ischemic injury through reducing neuronal apoptosis in mice.

BACKGROUND: Farnesoid X receptor (FXR) is a nuclear receptor that plays a critical role in controlling cell apoptosis in diverse diseases. Previous studies have shown that knocking out FXR improved cardiac function by reducing cardiomyocyte apoptosis in myocardial ischemic mice. However, the role of FXR after cerebral ischemia remains unknown. In this study, we explored the effects and mechanisms of FXR knockout (KO) on the functional recovery of mice post cerebral ischemia-reperfusion. METHODS: Adult male C57BL/6 wild type and FXR KO mice were subjected to 90-min transient middle cerebral artery occlusion (tMCAO). The mice were divided into five groups: sham, wild-type tMCAO, FXR KO tMCAO, wild-type tMCAO treated with calcium agonist Bayk8644, and FXR KO tMCAO treated with Bayk8644. FXR expression was examined using immunohistochemistry and Western blot. Brain infarct and brain atrophy volume were examined at 3 and 14 days after stroke respectively. Neurobehavioral tests were conducted up to 14 days after stroke. The protein levels of apoptotic factors (Bcl-2, Bax, and Cleaved caspase-3) and mRNA levels of pro-inflammatory factors (TNF-α, IL-6, IL-1ß, IL-17, and IL-18) were examined using Western blot and RT-PCR. TUNEL staining and calcium imaging were obtained using confocal and two-photon microscopy. RESULTS: The expression of FXR was upregulated after ischemic stroke, which is located in the nucleus of the neurons. FXR KO was found to reduce infarct volume and promote neurobehavioral recovery following tMCAO compared to the vehicle. The expression of apoptotic and pro-inflammatory factors decreased in FXR KO mice compared to the control. The number of NeuN+/TUNEL+ cells declined in the peri-infarct area of FXR KO mice compared to the vehicle. We further demonstrated that inhibition of FXR reduced calcium overload and addition of ionomycin could reverse this neuroprotective effect in vitro. What is more, in vivo results showed that enhancement of intracellular calcium concentrations could aggravate ischemic injury and reverse the neuroprotective effect of FXR KO in mice. CONCLUSIONS: FXR KO can promote neurobehavioral recovery and attenuate ischemic brain injury, inflammatory release, and neuronal apoptosis via reducing calcium influx, suggesting its role as a therapeutic target for stroke treatments.

Big data modeling to predict platelet usage and minimize wastage in a tertiary care system.

Maintaining a robust blood product supply is an essential requirement to guarantee optimal patient care in modern health care systems. However, daily blood product use is difficult to anticipate. Platelet products are the most variable in daily usage, have short shelf lives, and are also the most expensive to produce, test, and store. Due to the combination of absolute need, uncertain daily demand, and short shelf life, platelet products are frequently wasted due to expiration. Our aim is to build and validate a statistical model to forecast future platelet demand and thereby reduce wastage. We have investigated platelet usage patterns at our institution, and specifically interrogated the relationship between platelet usage and aggregated hospital-wide patient data over a recent consecutive 29-mo period. Using a convex statistical formulation, we have found that platelet usage is highly dependent on weekday/weekend pattern, number of patients with various abnormal complete blood count measurements, and location-specific hospital census data. We incorporated these relationships in a mathematical model to guide collection and ordering strategy. This model minimizes waste due to expiration while avoiding shortages; the number of remaining platelet units at the end of any day stays above 10 in our model during the same period. Compared with historical expiration rates during the same period, our model reduces the expiration rate from 10.5 to 3.2%. Extrapolating our results to the ∼2 million units of platelets transfused annually within the United States, if implemented successfully, our model can potentially save ∼80 million dollars in health care costs.

Dihydromyricetin protects HUVECs of oxidative damage induced by sodium nitroprusside through activating PI3K/Akt/FoxO3a signalling pathway.

The damage of vascular endothelial cells induced by oxidative stress plays an important role in the pathogenesis of atherosclerosis. Dihydromyricetin (DMY) is considered as a natural antioxidant. However, the mechanism of DMY on endothelial cell injury induced by oxidative stress remains unclear. In this study, we found that DMY could reduce the oxidative damage of HUVECs induced by sodium nitroprusside (SNP), HUVECs pre-treated with DMY suppressed SNP-induced apoptosis by reduced ROS overproduction of intracellular, decreased MDA level and elevated the superoxide dismutase activity. Meanwhile, we found that DMY could promote the expression of phosphorylated FoxO3a and Akt, and affect the nuclear localization of FoxO3a, when treated with the PI3K inhibitor LY294002, the effect of DMY was blocked. These data suggest that DMY protects HUVECs from oxidative stress by activating PI3K/Akt/FoxO3a signalling pathway. Therefore, DMY may have great therapeutic potential as a new drug for atherosclerosis.

Monitoring circulating tumor cells in vivo by a confocal microscopy system.

Circulating tumor cells (CTCs) play a key role in cancer metastasis but are very difficult to detect. in vivo monitoring CTCs has been recognized as an important technique for cancer research and clinical diagnosis. Recently, a noninvasive method, in vivo flow cytometry (IVFC) has been developed to enable continuous, real-time, and long-duration detection of CTCs in animal models by detecting CTC fluorescence in blood vessels excited by lasers. In this study, we present a simple optical scheme for direct noninvasive CTC detection using confocal microscopes. We demonstrate that line scanning of confocal microscopy can provide effective and quantitative CTC detection in live mice during cancer development. Rare CTC signals can be acquired at the early stage of the tumor development after implantation of subcutaneous tumor and monitored continuously to the end. Signals from CTC clusters can also be acquired and distinguished from single CTCs. Our results suggest confocal microscopy is a simple and reliable method for biologists and doctors to use for cancer research. © 2018 International Society for Advancement of Cytometry.

Polo-like kinase-1 triggers histone phosphorylation by Haspin in mitosis.

Histone modifications coordinate the chromatin localization of key regulatory factors in mitosis. For example, mitotic phosphorylation of Histone H3 threonine-3 (H3T3ph) by Haspin creates a binding site for the chromosomal passenger complex (CPC). However, how these histone modifications are spatiotemporally controlled during the cell cycle is unclear. Here we show that Plk1 binds to Haspin in a Cdk1-phosphorylation-dependent manner. Reducing Plk1 activity decreases the phosphorylation of Haspin and inhibits H3T3ph, particularly in prophase, suggesting that Plk1 is required for initial activation of Haspin in early mitosis. These studies demonstrate that Plk1 can positively regulate CPC recruitment in mitosis.

Electrocardiogram Signal Denoising Using Extreme-Point Symmetric Mode Decomposition and Nonlocal Means.

Electrocardiogram (ECG) signals contain a great deal of essential information which can be utilized by physicians for the diagnosis of heart diseases. Unfortunately, ECG signals are inevitably corrupted by noise which will severely affect the accuracy of cardiovascular disease diagnosis. Existing ECG signal denoising methods based on wavelet shrinkage, empirical mode decomposition and nonlocal means (NLM) cannot provide sufficient noise reduction or well-detailed preservation, especially with high noise corruption. To address this problem, we have proposed a hybrid ECG signal denoising scheme by combining extreme-point symmetric mode decomposition (ESMD) with NLM. In the proposed method, the noisy ECG signals will first be decomposed into several intrinsic mode functions (IMFs) and adaptive global mean using ESMD. Then, the first several IMFs will be filtered by the NLM method according to the frequency of IMFs while the QRS complex detected from these IMFs as the dominant feature of the ECG signal and the remaining IMFs will be left unprocessed. The denoised IMFs and unprocessed IMFs are combined to produce the final denoised ECG signals. Experiments on both simulated ECG signals and real ECG signals from the MIT-BIH database demonstrate that the proposed method can suppress noise in ECG signals effectively while preserving the details very well, and it outperforms several state-of-the-art ECG signal denoising methods in terms of signal-to-noise ratio (SNR), root mean squared error (RMSE), percent root mean square difference (PRD) and mean opinion score (MOS) error index.

Unusual calcifying fibrous tumor in the fallopian tube: review and discussion of the differential diagnosis.

Calcifying fibrous tumor (CFT) is a rare benign soft tissue tumor of unknown etiology and extremely rare in female reproductive system. We present a case of unusual CFT in the ampulla of fallopian tube occurring in a middle-aged female patient with multiple uterine leiomyomas. A hysterectomy was performed on a 48-year-old woman for uterine leiomyomas. At surgery, a solitary, well-defined nodule, measuring 1.0 cm in diameter, was incidentally observed on the wall of ampulla of right fallopian tube. The lesion of fallopian tube was resected totally. Histologically, this lesion was unencapsulated and composed of hyalinized collagenous fibrous tissue with psammomatous calcification and focal lymphoplasmacytic infiltrate. Sparsely fibroblast-like spindle cells were scattered in the dense hyalinized background with bland nuclei. By immunohistochemistry, vimentin was diffusely positive in most cells, and a focal reactivity for CD34 was also observed in spindle cells. However, they were negative for cytokeratin (AE1/AE3), S-100 protein, CD117, DOG1, SMA, desmin, and ALK. The Ki-67 labeling index of the lesion was <1%. A diagnosis of primary CFT of fallopian tube was made. To our knowledge, this is the first report of CFT occurring in female reproductive tract. Awareness of CFT and its distinctive features is important to avoid a diagnostic pitfall caused by histologic similarities to other spindle cell or calcifying lesions in unusual locations. Although marginal excision is usually adequate for most of CFT, long-term follow-up is suggested as delayed recurrence might occur infrequently.

Increased expression of macrophage migration inhibitory factor and DJ-1 contribute to cell invasion and metastasis of nasopharyngeal carcinoma.

BACKGROUND AND AIM: Both macrophage migration inhibitory factor (MIF) and DJ-1 protein have been shown to relate with cell invasion and metastasis in tumors. However, the role of DJ-1 in invasion and metastasis of nasopharyngeal carcinoma (NPC) and its relation to MIF expression in NPC are not fully understood. The aim of present study is to determine whether or not MIF and DJ-1 are correlated with tumor invasion and influence a worse outcome in NPC, as well as its related mechanism. METHODS: 125 cases of NPC and 45 normal tissues of nasopharynx were collected. The expression of MIF and DJ-1 in tissue microarray was evaluated by immunohistochemical staining. Correlation between immunostainings and clinicopathological parameters, as well as the follow-up data of patients, was analyzed statistically. The association of MIF and DJ-1 with cell invasion and migration in NPC cell line were evaluated by small interfering RNA (siRNA) transfection, invasion assay and Western blotting. RESULTS: MIF and DJ-1 staining was diffused and strong in tumor cells, whereas they were generally weaker and less common in normal lining epithelia of nasopharynx. High MIF expression in tumor cells (71.2%, 89/125 cases) were significantly associated with advanced clinical stage, lymph node metastasis, and worse prognosis of NPC patients. High expression of DJ-1 (75.2%, 94/125 cases) were closely correlated to lymph node metastasis and MIF high-expression. Only MIF high expression (P = 0.010) and lymph node metastasis (P = 0.004) emerged as strong independent prognostic factors for overall survival of NPC patients. In vitro, down-regulated expression of DJ-1 in NPC cell lines by siRNA was observed to reduce cell migration and invasion potential, however, exogenous MIF promoted cells invasion. CONCLUSIONS: The data provided evidence that increased expression of MIF and DJ-1 induced cell invasion and metastasis of NPC, supporting the idea that MIF and DJ-1 may play important roles as regulators in the progression of NPC.

Intraspinal dural-based primary osteoblastoma with aneurysmal bone cyst-like change.

Osteoblastoma is a benign bone-forming neoplasm that occurs commonly in the posterior elements of the spine and the sacrum. However, so far there has been no report of intradural osteoblastoma described in the literature. We present a unique case of intraspinal dural-based osteoblastoma with aneurysmal bone cyst-like change without evidence of vertebral involvement. An 11-year-old Chinese girl presented with a 3-month history of gradually progressive back pain and a weakness of both lower limbs. Thoracic MRI revealed a well-demarcated subdural mass at the T5 level with heterogeneous enhancement. Histologically, the tumor was found to be attached to the dura and composed of numerous osteoid spicules and trabecular bone with diffusely scattered osteoclast-type, multinucleated giant cells. Ectactic blood vessels and blood-filled cystic spaces were also observed. A diagnosis of primary intraspinal dural-based osteoblastoma with aneurysmal bone cyst-like change was made. To our best knowledge, this is possibly the first case of primary osteoblastoma arising from meninges. Meningeal osteocartilaginous tumors are rare, with obscure histogenesis. The differential diagnosis of osteoblastoma in unusual locations is difficult and the confirmation of diagnosis should be cautiously made. Awareness of dural-based osteoblastoma and its histological features is important to avoid a diagnostic pitfall caused by histological similarities to other intra-craniospinal lesions with osteoid differentiation or bone formation.

DJ-1 is activated in medulloblastoma and is associated with cell proliferation and differentiation.

BACKGROUND: DJ-1 is a key regulator in human tumorigenesis, including brain malignancies. The mechanisms by which DJ-1 contributes to the pathogenesis of medulloblastoma (MB) remain unclear, and its impact on the prognosis for patients with MB has not been identified. The aim of this study was to determine whether the DJ-1 protein is associated with tumorigenesis of MBs, and whether DJ-1 is a valuable factor for predicting the prognosis of patients with MB. METHODS: We collected 66 pairs of MB and adjacent normal cerebellum samples. Expression of DJ-1, Ser 473-phosphorylated-Akt (p-Akt), PTEN, and Ki-67 (MIB-1) was detected by immunohistochemical staining, and the correlation of these immunostaining results with the clinicopathological features of patients with MB was determined. RESULTS: High DJ-1 expression (48.5%, 32/66) in tumor cells of MBs was significantly associated with the classic MB variant (P = 0.003), high proliferative activity (P = 0.002) and undifferentiated tumor (P = 0.001), whereas high p-Akt expression (56.1%, 37/66) was associated with tumor metastasis stage (P = 0.007), undifferentiated tumor (P = 0.007), and high-risk tumor (P = 0.002). High DJ-1 expression also correlated with high p-Akt expression and high MIB-1 index. However, only high levels of DJ-1(P = 0.009) and high MIB-1 index (P = 0.001) were strong independent prognostic factors associated with worse overall survival. CONCLUSIONS: Although the validity of the preliminary data in this study needs to be confirmed by a larger number of cases, our study indicates that DJ-1, PTEN, and p-Akt might play important roles in cell proliferation and differentiation of MBs. The evaluation of expression of DJ-1 and related proteins might be useful for predicting the prognosis of patients with MB.

Electrocardiographic abnormalities in patients with microtia.

The main objective of this study was to investigate the incidence and characteristics of electrocardiographic abnormalities in patients with microtia, and to explore cardiac maldevelopment associated with microtia. This retrospective study analyzed a large cohort of microtia patients admitted to Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from September 2017 to August 2022. The routine electrocardiographic reports of these patients were reviewed to assess the incidence and characteristics of abnormalities. The study included a total of 10,151 patients (5598 in the microtia group and 4553 in the control group) who were admitted to the Plastic Surgery Hospital of Peking Union Medical College. The microtia group had a significantly higher incidence of abnormal electrocardiographies compared to the control group (18.3% vs. 13.6%, P < 0.01), even when excluding sinus irregularity (6.1% vs. 4.4%, P < 0.01). Among the 1025 cases of abnormal electrocardiographies in the microtia group, 686 cases were reported with simple sinus irregularity. After excluding sinus irregularity as abnormal, the most prevalent abnormalities was right bundle branch block (37.5%), followed by sinus bradycardia (17.4%), ST-T wave abnormalities (13.3%), atrial rhythm (9.1%), sinus tachycardia (8.3%), and ventricular high voltage (4.7%). Less common ECG abnormalities included atrial tachycardia (2.1%), ventricular premature contraction (2.4%), and ectopic atrial rhythm (1.8%). atrioventricular block and junctional rhythm were present in 1.2% and 0.9% of the cases, respectively. Wolff Parkinson White syndrome and dextrocardia had a lower prevalence, at 0.6% and 0.9%, respectively. The occurrence of electrocardiographic abnormalities in microtia patients was found to be higher compared to the control group. These findings highlight the potential congenital defect in cardiac electrophysiology beyond the presence of congenital heart defect that coincide with microtia.